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4-110476522-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001977.4(ENPEP):c.108C>T(p.Ala36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,603,474 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 190 hom., cov: 32)
Exomes 𝑓: 0.0029 ( 181 hom. )

Consequence

ENPEP
NM_001977.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.94
Variant links:
Genes affected
ENPEP (HGNC:3355): (glutamyl aminopeptidase) The ENPEP gene encodes glutamyl aminopeptidase, a type II integral membrane protein with an extracellular zinc-binding domain. This protein can upregulate blood pressure by cleaving the N-terminal aspartate from angiotensin II, and can regulate blood vessel formation and enhance tumorigenesis in some tissues. Along with ANPEP and DPP4, ENPEP was found to be a candidate co-receptor for the coronavirus SARS-CoV-2, which causes COVID-19. [provided by RefSeq, Apr 2020]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-110476522-C-T is Benign according to our data. Variant chr4-110476522-C-T is described in ClinVar as [Benign]. Clinvar id is 780491.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-5.94 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0891 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ENPEPNM_001977.4 linkuse as main transcriptc.108C>T p.Ala36= synonymous_variant 1/20 ENST00000265162.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ENPEPENST00000265162.10 linkuse as main transcriptc.108C>T p.Ala36= synonymous_variant 1/201 NM_001977.4 P1
ENPEPENST00000510961.1 linkuse as main transcriptn.73-12019C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0264
AC:
4014
AN:
152100
Hom.:
189
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0915
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0106
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000367
Gnomad OTH
AF:
0.0158
GnomAD3 exomes
AF:
0.00695
AC:
1706
AN:
245502
Hom.:
66
AF XY:
0.00528
AC XY:
699
AN XY:
132330
show subpopulations
Gnomad AFR exome
AF:
0.0913
Gnomad AMR exome
AF:
0.00476
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000137
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000306
Gnomad OTH exome
AF:
0.00402
GnomAD4 exome
AF:
0.00286
AC:
4146
AN:
1451256
Hom.:
181
Cov.:
30
AF XY:
0.00251
AC XY:
1811
AN XY:
720208
show subpopulations
Gnomad4 AFR exome
AF:
0.0973
Gnomad4 AMR exome
AF:
0.00519
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.000153
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000232
Gnomad4 OTH exome
AF:
0.00602
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0264
AC:
4024
AN:
152218
Hom.:
190
Cov.:
32
AF XY:
0.0263
AC XY:
1961
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0916
Gnomad4 AMR
AF:
0.0105
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000368
Gnomad4 OTH
AF:
0.0156
Alfa
AF:
0.0136
Hom.:
38
Bravo
AF:
0.0303
Asia WGS
AF:
0.00520
AC:
19
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
0.61
Dann
Benign
0.78

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76248418; hg19: chr4-111397678; API